Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Abstract

Abstract. Stem cells are known to differentiate in response toHowever, identification of these stem cell inducing molecules is non-trivial and rational approaches to discover drugs for achieving reproducible, targeted stem cell control remain elusive. Here, we demonstrate the design of supramolecular hydrogels that allow targeting of a range of stem cell phenotypes, providing a useful platform for discovery of differentiation inducing metabolites. These gels are simple in composition, containing a fibre forming aromatic peptide amphiphile, which is coassembled with a surfactant-like amphiphile that provides hydrophilic surface functionality to the fibres. The stiffness of the gels can be precisely tuned over the entire range that is typically associated with stem cell differentiation (0.1-40 kPa). 3We demonstrate that the gels can be used to direct stem cell differentiation without the need for induction media and they are therefore ideally suited to study stem cell behaviour -including as drug discovery platforms. To achieve this, we study the cell's usage of biological small molecules, metabolites, during differentiation and select bioactive metabolites that can target bone and cartilage formation specifically. This new use of designed supramolecular biomaterials can be envisaged to remove serendipity from discovery of metabolites associated with biological processes as drug candidates. Introduction.

Low-Molecular-Weight Gels: The State of the Art

“…[8][9][10][11][12] The specific self-assembly leading to gel formation can be exploited. For example, the fiber formation is a result of molecular stacking, meaning that the self-assembly leads to aggregates that can be suitable for optoelectronic applications.…”

Supramolecular materials

“…7 If allowed long enough to equilibrate 25 and with appropriate energy to allow mass transport, defects and metastable states are engulfed in the bulk stable phase, by the kind of process exemplified by Ostwald ripening. Liquid crystals -that are fluids with orientational order but positional disorder -are perhaps the materials with the broadest scope and 30 application presently where the equilibrium structures are determined by the relatively weak interactions between molecules, though strong interactions can influence the shape and dimensions of the units that assemble to give the nematic, smectic or discotic phases (Fig. 2).…”

“…1). Indeed, because of their short lifetimes on the archaeological timescale, soft materials are the often forgotten component of human 30 progress. Soft materials comprising molecule-based systems have gradually found applications in all kinds of everyday machines and devices, with supramolecular chemistry playing an increasingly evident role, 1 as it does in natural systems.…”

Digital biomanufacturing supporting vascularization in 3D bioprinting

“…Until quite recently, all the structural material components of bioinks were adopted from other applications. However, some characterized products and bioprinting qualified materials are now becoming commercially available [16,17] . The cell-culture components have been supplied by commercialized culture media formulations and most-often include serum.…”